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Temozolomide With or Without Veliparib in Treating Patients With Relapsed or Refractory Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT01638546
Recruitment Status : Completed
First Posted : July 11, 2012
Results First Posted : March 27, 2018
Last Update Posted : June 7, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Recurrent Small Cell Lung Carcinoma
Interventions Other: Laboratory Biomarker Analysis
Other: Placebo
Drug: Temozolomide
Drug: Veliparib
Enrollment 97
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm I (Veliparib and Temozolomide) Arm II (Placebo and Temozolomide)
Hide Arm/Group Description

Patients receive veliparib PO BID on days 1-7 and temozolomide PO on days 1-5.

Laboratory Biomarker Analysis: Correlative studies

Temozolomide: Given PO

Veliparib: Given PO

Patients receive placebo PO BID on days 1-7 and temozolomide as in Arm I.

Laboratory Biomarker Analysis: Correlative studies

Placebo: Given PO

Temozolomide: Given PO

Period Title: Overall Study
Started 52 45
Completed 51 42
Not Completed 1 3
Reason Not Completed
Adverse Event             1             3
Arm/Group Title Arm I (Veliparib and Temozolomide) Arm II (Placebo and Temozolomide) Total
Hide Arm/Group Description

Patients receive veliparib PO BID on days 1-7 and temozolomide PO on days 1-5.

Laboratory Biomarker Analysis: Correlative studies

Temozolomide: Given PO

Veliparib: Given PO

Patients receive placebo PO BID on days 1-7 and temozolomide as in Arm I.

Laboratory Biomarker Analysis: Correlative studies

Placebo: Given PO

Temozolomide: Given PO

Total of all reporting groups
Overall Number of Baseline Participants 52 45 97
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 45 participants 97 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
31
  59.6%
31
  68.9%
62
  63.9%
>=65 years
21
  40.4%
14
  31.1%
35
  36.1%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 45 participants 97 participants
Female
29
  55.8%
23
  51.1%
52
  53.6%
Male
23
  44.2%
22
  48.9%
45
  46.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 45 participants 97 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
4
   7.7%
1
   2.2%
5
   5.2%
White
47
  90.4%
43
  95.6%
90
  92.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   1.9%
1
   2.2%
2
   2.1%
1.Primary Outcome
Title Progression-free Survival, Calculated as the Proportion of Patients Alive and Without Evidence of Disease
Hide Description Compared across the two arms using a Fisher exact test.
Time Frame From randomization to time of progression or death, whichever occurs first, assessed at 4 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (Veliparib and Temozolomide) Arm II (Placebo and Temozolomide)
Hide Arm/Group Description:

Patients receive veliparib PO BID on days 1-7 and temozolomide PO on days 1-5.

Laboratory Biomarker Analysis: Correlative studies

Temozolomide: Given PO

Veliparib: Given PO

Patients receive placebo PO BID on days 1-7 and temozolomide as in Arm I.

Laboratory Biomarker Analysis: Correlative studies

Placebo: Given PO

Temozolomide: Given PO

Overall Number of Participants Analyzed 51 42
Measure Type: Number
Unit of Measure: percentage of participants
36 27
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I (Veliparib and Temozolomide), Arm II (Placebo and Temozolomide)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
2.Secondary Outcome
Title ORR by RECIST 1.1 Criteria
Hide Description Corresponding exact two-sided 95% confidence intervals will be calculated and reported in both arms of the study. Comparisons between treatment arms will be performed using Fisher-exact test.
Time Frame Assessed up to 5 years
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Overall Survival
Hide Description Estimated in each treatment group using Kaplan-Meier method. Group comparisons will be performed using log-rank test.
Time Frame From randomization to time of death, assessed up to 5 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (Veliparib and Temozolomide) Arm II (Placebo and Temozolomide)
Hide Arm/Group Description:

Patients receive veliparib PO BID on days 1-7 and temozolomide PO on days 1-5.

Laboratory Biomarker Analysis: Correlative studies

Temozolomide: Given PO

Veliparib: Given PO

Patients receive placebo PO BID on days 1-7 and temozolomide as in Arm I.

Laboratory Biomarker Analysis: Correlative studies

Placebo: Given PO

Temozolomide: Given PO

Overall Number of Participants Analyzed 51 42
Median (95% Confidence Interval)
Unit of Measure: months
8.2
(6.4 to 12.2)
7
(5.3 to 9.5)
4.Other Pre-specified Outcome
Title BRCA1 Expression, Assessed by Immunohistochemistry
Hide Description Fisher's exact test will be used to correlate response and log-rank test to correlate with progression free survival and overall survival.
Time Frame Up to 5 years
Outcome Measure Data Not Reported
5.Other Pre-specified Outcome
Title Changes in Plasma Markers
Hide Description Correlated with outcome in the two treatment arms.
Time Frame Baseline to up to 5 years
Outcome Measure Data Not Reported
6.Other Pre-specified Outcome
Title GammaH2AX Levels
Hide Description Wilcoxon test will be used to compare the percentage increase of gammaH2AX positive cells between the two treatment groups.
Time Frame Up to 5 years
Outcome Measure Data Not Reported
7.Other Pre-specified Outcome
Title MGMT Expression, Assessed by Immunohistochemistry
Hide Description Results will be expressed as binary variables. Associations with objective response, with progression free survival and with overall survival will be tested using Fisher's exact test and log-rank test, respectively.
Time Frame Up to 5 years
Outcome Measure Data Not Reported
8.Other Pre-specified Outcome
Title Number of Circulating Tumor Cells
Hide Description The number of CTCs will be correlated with PFS and OS using Cox proportional hazards model. The change in CTCs will be correlated with radiographic response. The number of CTCs at baseline will be correlated with patient characteristics (disease burden, location of metastases, and progression at existing sites or new sites of disease). The number of CTC will be explored as a continuous variable and the presence of a threshold predictive of the outcome will be investigated.
Time Frame Up to 5 years
Outcome Measure Data Not Reported
9.Other Pre-specified Outcome
Title PARP-1 Expression
Hide Description Fisher's exact test will be used to correlate response and log-rank test to correlate with progression free survival and overall survival.
Time Frame Up to 5 years
Outcome Measure Data Not Reported
10.Other Pre-specified Outcome
Title Presence of MGMT Promoter Methylation, Assessed by the EpiTyper Assay
Hide Description Results will be expressed as binary variables. Associations with objective response, with progression free survival and with overall survival will be tested using Fisher's exact test and log-rank test, respectively.
Time Frame Up to 5 years
Outcome Measure Data Not Reported
11.Other Pre-specified Outcome
Title PTEN Expression, Assessed by Immunohistochemistry
Hide Description Fisher's exact test will be used to correlate response and log-rank test to correlate with progression free survival and overall survival.
Time Frame Up to 5 years
Outcome Measure Data Not Reported
12.Other Pre-specified Outcome
Title RAD51 Expression, Assessed by Immunohistochemistry
Hide Description Fisher's exact test will be used to correlate response and log-rank test to correlate with progression free survival and overall survival.
Time Frame Up to 5 years
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm I (Veliparib and Temozolomide) Arm II (Placebo and Temozolomide)
Hide Arm/Group Description

Patients receive veliparib PO BID on days 1-7 and temozolomide PO on days 1-5.

Laboratory Biomarker Analysis: Correlative studies

Temozolomide: Given PO

Veliparib: Given PO

Patients receive placebo PO BID on days 1-7 and temozolomide as in Arm I.

Laboratory Biomarker Analysis: Correlative studies

Placebo: Given PO

Temozolomide: Given PO

All-Cause Mortality
Arm I (Veliparib and Temozolomide) Arm II (Placebo and Temozolomide)
Affected / at Risk (%) Affected / at Risk (%)
Total   41/52 (78.85%)      39/45 (86.67%)    
Show Serious Adverse Events Hide Serious Adverse Events
Arm I (Veliparib and Temozolomide) Arm II (Placebo and Temozolomide)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   22/52 (42.31%)      18/45 (40.00%)    
Cardiac disorders     
Heart failure  1  0/52 (0.00%)  0 1/45 (2.22%)  1
Pericardial effusion  1  0/52 (0.00%)  0 1/45 (2.22%)  1
Ventricular tachycardia  1  1/52 (1.92%)  1 0/45 (0.00%)  0
Ear and labyrinth disorders     
Fall  1  1/52 (1.92%)  2 0/45 (0.00%)  0
Gait disturbance  1  1/52 (1.92%)  1 0/45 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain  1  2/52 (3.85%)  2 1/45 (2.22%)  1
Anorexia  1  0/52 (0.00%)  0 1/45 (2.22%)  1
Dehydration  1  0/52 (0.00%)  0 1/45 (2.22%)  1
Gastric perforation  1  0/52 (0.00%)  0 1/45 (2.22%)  1
Nausea  1  0/52 (0.00%)  0 1/45 (2.22%)  1
Vomiting  1  0/52 (0.00%)  0 2/45 (4.44%)  2
Appendicitis perforated  1  1/52 (1.92%)  1 0/45 (0.00%)  0
Diarrhea  1  1/52 (1.92%)  1 0/45 (0.00%)  0
Hepatic failure  1  1/52 (1.92%)  1 0/45 (0.00%)  0
General disorders     
Fatigue  1  0/52 (0.00%)  0 1/45 (2.22%)  1
Sepsis  1  2/52 (3.85%)  2 0/45 (0.00%)  0
Investigations     
Febrile Neutropenia  1  3/52 (5.77%)  3 0/45 (0.00%)  0
Neutrophil count decreased  1  1/52 (1.92%)  1 0/45 (0.00%)  0
Platelet count decreased  1  5/52 (9.62%)  5 0/45 (0.00%)  0
White blood cell decreased  1  2/52 (3.85%)  2 0/45 (0.00%)  0
Metabolism and nutrition disorders     
Hyponatremia  1  1/52 (1.92%)  1 2/45 (4.44%)  2
Hypophosphatemia  1  0/52 (0.00%)  0 1/45 (2.22%)  2
Anemia  1  2/52 (3.85%)  2 0/45 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain  1  1/52 (1.92%)  1 0/45 (0.00%)  0
Hip fracture  1  1/52 (1.92%)  1 0/45 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Neoplasms ben/mal/unk (inc cyst/polyp) Other, spec  1  2/52 (3.85%)  2 3/45 (6.67%)  3
Nervous system disorders     
Nervous system disorders - Other, specify  1  3/52 (5.77%)  3 0/45 (0.00%)  0
Renal and urinary disorders     
Acute Kidney Injury  1  0/52 (0.00%)  0 1/45 (2.22%)  1
Urinary retention  1  1/52 (1.92%)  1 0/45 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Dyspnea  1  2/52 (3.85%)  2 2/45 (4.44%)  2
Pleural effusion  1  0/52 (0.00%)  0 2/45 (4.44%)  2
Respiratory failure  1  0/52 (0.00%)  0 1/45 (2.22%)  1
Bronchopulmonary hemorrhage  1  1/52 (1.92%)  1 0/45 (0.00%)  0
Lung infection  1  2/52 (3.85%)  5 0/45 (0.00%)  0
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm I (Veliparib and Temozolomide) Arm II (Placebo and Temozolomide)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/52 (11.54%)      35/45 (77.78%)    
Blood and lymphatic system disorders     
Platelet count decreased  1  5/52 (9.62%)  14/45 (31.11%) 
Alanine aminotransferase increased  1  0/52 (0.00%)  8/45 (17.78%) 
Anemia  1  0/52 (0.00%)  18/45 (40.00%) 
Aspartate aminotransferase increased  1  0/52 (0.00%)  3/45 (6.67%) 
Lymphocyte count decreased  1  0/52 (0.00%)  23/45 (51.11%) 
Neutrophil count decreased  1  0/52 (0.00%)  6/45 (13.33%) 
White blood cell decreased  1  0/52 (0.00%)  9/45 (20.00%) 
General disorders     
Febrile neutropenia  1  3/52 (5.77%)  0/45 (0.00%) 
Anorexia  1  0/52 (0.00%)  3/45 (6.67%) 
Fatigue  1  0/52 (0.00%)  13/45 (28.89%) 
Nausea  1  0/52 (0.00%)  3/45 (6.67%) 
Metabolism and nutrition disorders     
Alkaline phosphatase increased  1  0/52 (0.00%)  6/45 (13.33%) 
Hyperglycemia  1  0/52 (0.00%)  14/45 (31.11%) 
Hypoalbuminemia  1  0/52 (0.00%)  5/45 (11.11%) 
Hypocalcemia  1  0/52 (0.00%)  7/45 (15.56%) 
Creatinine increased  1  0/52 (0.00%)  3/45 (6.67%) 
Hyponatremia  1  0/52 (0.00%)  3/45 (6.67%) 
Hypophosphatemia  1  0/52 (0.00%)  4/45 (8.89%) 
Lipase increased  1  0/52 (0.00%)  4/45 (8.89%) 
Serum amylase increased  1  0/52 (0.00%)  3/45 (6.67%) 
Nervous system disorders     
Nervous system disorders - Other, specify  1  3/52 (5.77%)  0/45 (0.00%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Charles Rudin
Organization: Memorial Sloan Kettering Cancer Center
Phone: 646-888-4527
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01638546     History of Changes
Other Study ID Numbers: NCI-2012-01130
NCI-2012-01130 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
IRB #12-021
12-021
CDR0000737062
9026 ( Other Identifier: Memorial Sloan-Kettering Cancer Center )
9026 ( Other Identifier: CTEP )
N01CM00039 ( U.S. NIH Grant/Contract )
P30CA008748 ( U.S. NIH Grant/Contract )
U01CA070095 ( U.S. NIH Grant/Contract )
UM1CA186691 ( U.S. NIH Grant/Contract )
First Submitted: July 9, 2012
First Posted: July 11, 2012
Results First Submitted: February 27, 2018
Results First Posted: March 27, 2018
Last Update Posted: June 7, 2018